OBJECTIVE: To explore the serological and molecular genetic characteristics of a family with subtype B(A)06. METHODS: A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036). RESULTS: The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family. CONCLUSION The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans ; ABO Blood-Group System/genetics* ; Female ; Pedigree ; Male ; Infant, Newborn ; Asian People/genetics* ; Genotype ; China ; Blood Grouping and Crossmatching ; Hyperbilirubinemia, Neonatal/blood* ; East Asian People

Cerebrovascular disease is uncommon in patients with HIV, occurring in up to 1.9% of patients, 0.2% were presenting with transient ischemic attacks. The central nervous system is the first part of the body to be affected by the human immunodeficiency virus. This case report is a unique presentation of a 33-year-old male who presented with focal neurologic deficits that lasted for one hour with a background of promiscuous history. The patient was positive for HIV screening test and CD4 count and was started on a combination of antiretroviral therapy. This is the first documented case report in the Philippines. This case report demonstrates the need for a high index of suspicion for early detection of the cause in HIV-positive patients with recurrent transient ischemic attacks, given the high morbidity and mortality that is associated with this condition if delayed or undiagnosed.

Abstract Hyperkalemia (serum potassium >5.0 mEq/l) is a significant complication in patients with heart failure, chronic kidney disease, and diabetes mellitus, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Both hyperkalemia and RAASi interruption are associated with increased cardiovascular events, hospitalizations, and mortality. This expert opinion document, developed between January and December 2024 through a systematic process, aims to establish guidance for hyperkalemia treatment in Indonesian patients with cardiorenal diseases receiving RAASi therapy, addressing the unique challenges within the Indonesian healthcare context. A comprehensive literature review of international guidelines and regional studies was conducted by a panel of 11 expert specialists (3 cardiologists, 6 internist-nephrologists, and 2 internist-cardiologists), who evaluated 29 statements covering diagnosis, monitoring, prevention, and treatment of hyperkalemia. Of the 29 statements, 26 reached consensus: 17 statements achieved very high agreement (≥90%) and 9 attained high agreement (≥67% – <90%). The agreed statements covered key areas, including potassium monitoring frequency, RAASi dose optimization strategies, dietary modifications, and treatment thresholds. Three statements regarding alternative therapeutic approaches did not receive agreement (<67%) due to limited local availability and cost considerations. Key recommendations include structured monitoring protocols for high-risk patients, strategies for RAASi dose optimization while managing hyperkalemia risk, and specific interventions adapted to local resources. This document provides a practical approach for managing hyperkalemia in Indonesian patients with cardiorenal diseases while maintaining optimal RAASi therapy, considering local Indonesian healthcare resources and constraints.
Hyperkalemia ; Cardio-Renal Syndrome ; Renin-Angiotensin System ; Indonesia

Introduction: Central precocious puberty (CPP) is defined as premature activation of the hypothalamic-pituitary-gonadal axis, resulting in the development of secondary sexual characteristics before 8 years of age in girls. While most cases are idiopathic, intracranial pathologies such as pituitary lesions may cause CPP. Early identification is essential to optimize outcomes and minimize psychosocial impact. We report a case of CPP associated with pituitary microadenoma and pineal cyst from the Paediatric Department, Hospital Sultanah Nur Zahirah. Case: A 4-year-old female presented with bilateral breast enlargement, with ultrasonography showing normal fibroglandular tissue. Breast development was noted since 3 months of age, with whitish vaginal discharge from 2 years. She demonstrated accelerated growth, with height and weight above the 95th centile. There were no features suggestive of peripheral causes or raised intracranial pressure. Examination revealed Tanner stage A1B3P2. Bone age was markedly advanced (11 years vs. chronological age 4 years). Hormonal evaluation showed elevated LH (3.28 IU/L) and follicle-stimulating hormone (4.79 IU/L), consistent with CPP. MRI demonstrated focal delayed enhancement in the posterolateral pituitary suggestive of microadenoma, and an incidental pineal cyst without complex features. Ophthalmological assessment was normal. Neurosurgical evaluation advised conservative management with annual imaging surveillance. Intramuscular Triptorelin was initiated at 4 years 1 month. Follow-up showed regression of pubertal progression, resolution of vaginal discharge, and reduced growth velocity to 6 cm/year. Conclusion This case highlights the importance of thorough evaluation in CPP to identify underlying intracranial pathology. Early initiation of gonadotropin-releasing hormone analog therapy effectively halts pubertal progression and preserves growth potential.
Central Nervous System Cysts ; Puberty

Cough is a very common symptom causing medical consult. Several remedies are readily available in the market however these are currently not recommended among the pediatric population due to a few reasons which include the benign nature of acute cough, limited effectivity and lack of support from the United States Food and Drug Administration (USFDA) due to abuse potential.

We report a case of a 2-year-old male, no known co-morbidities with a 2 week history of upper respiratory tract infection. Initial assessment showed viral infection hence patient was given medications for symptomatic treatment. However, l week after, patient still presented with symptomatic persistent coughing that disrupted his activities of daily living, hence antitussive medication was already prescribed. After another 7 days, there was still persistence of symptoms, hence patient was given a trial medication of Pregabalin 0.7 milligram/kg/dose which noted instant cough relief one hour after the initial intake. Patient also reported to be more playful, improved sleep at night and improved appetite. Patient received total of 2 doses of Pregabalin in the span of 48 hours. On the third day, patient was still coughing but reported to be significantly less frequent and more productive, hence medication was then put on hold. Patient continuously improved after 5 more days and was eventually cough free.

This case report demonstrates the adequacy of Pregabalin as a supportive antitussive medication in a patient with an acute cough secondary to a viral infection.

OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans ; Biomechanical Phenomena ; Orthopedics ; Traumatology ; Software ; Medicine, Chinese Traditional ; Musculoskeletal System ; Models, Biological

OBJECTIVE: To analyze the influences of dihydromyricetin on the proliferation and apoptosis of chondrocytes in osteoarthritis induced by hydrogen peroxide (H₂O₂) through reactive oxygen species (ROS)/p38 mitogen activated protein kinase (p38-MAPK) pathway. METHODS: Five C57BL/6J mice were euthanized by cervical dislocation after anesthesia. Chondrocytes were extracted and cultured.After passage, the chondrocytes were divided into control group, H2O2 group (0.8 μmol·L^-1 H₂O₂), dihydromyricetin low concentration group (0.8 μmol·L^-1 H₂O₂+20 μmol·L^-1 dihydromyricetin), dihydromyricetin high concentration group (0.8 μmol·L^-1 H₂O₂+80 μmol·L^-1 dihydromyricetin), and ROS inhibitor N-acetylcysteine (NAC) group (0.8 μmol·L^-1 H₂O₂+5 mmol·L^-1 NAC). The activity of chondrocytes was measured by methyl thiazolyl tetrazolium (MTT) assay. The apoptosis rate of chondrocytes was measured by Hoechst 33342 method. The level of ROS in chondrocytes was measured by 2, 7-dichlorofluorescein diacetate (DCFH-DA) fluorescence probe.The level of Type II collagen α1 (Col2α1) mRNA was measured by qRT-PCR.And the expression of Col2α1, p-p38-MAPK/p38-MAPK, B cell lymphoma gene-2 (Bcl-2) and Bcl-2 associated X protein (Bax) proteins was detected by Western blot. RESULTS: The chondrocytes showed swirling fibrous mass, and the expression of COL2α was positive. Compared with the control group, the chondrocyte viability, apoptosis rate, ROS fluorescence intensity, p-p38-MAPK/p38-MAPK, and the expression of Bax protein in H2O22 group increased, the level of Col2α1 mRNA, and the expression of Col2α1 and Bcl-2 proteins decreased (P<0.05). Compared with H₂O₂ group, the chondrocyte viability, apoptosis rate, ROS fluorescence intensity, p-p38-MAPK/p38-MAPK, and the expression of Bax protein in dihydromyricetin low concentration group, dihydromyricetin high concentration group, and NAC group decreased, the level of Col2α1 mRNA, and the expression of Col2α1 and Bcl-2 proteins increased (P<0.05). CONCLUSION Dihydromyricetin may inhibit chondrocyte apoptosis, inflammatory reaction and oxidative stress by inhibiting ROS/p38-MAPK pathway. Dihydromyricetin may be a potential drug for treating osteoarthritis.
Animals ; Chondrocytes/metabolism* ; Apoptosis/drug effects* ; Hydrogen Peroxide/toxicity* ; Osteoarthritis/physiopathology* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Mice ; Flavonols/pharmacology* ; p38 Mitogen-Activated Protein Kinases/genetics* ; Cell Proliferation/drug effects* ; Male ; Signal Transduction/drug effects* ; MAP Kinase Signaling System/drug effects* ; Cells, Cultured

Objective To precisely identify the para-Bombay blood types in cancer patients at our hospital, establish a robust system for the identification of challenging blood types in our laboratory, and provide a foundation for precise transfusion practices. Methods We retrospectively analyzed the blood type results of 91 874 cancer patients from January 1, 2019, to December 31, 2023. Conventional serological methods were used to screen for blood types, and suspected para-Bombay blood types were identified. Further analysis was performed using Pacific Biosciences (PacBio) single-molecule real-time sequencing and Sanger sequencing was used to determine the genotypes of the ABO, FUT1, and FUT2 genes. Results Eight cases of para-Bombay blood type were confirmed through serological and molecular biological methods. The FUT1 genotypes identified were: 5 cases of h1h1 (homozygous mutation 551_552delAG) and 3 cases of h1h2 (compound heterozygous mutations of 551_552delAG and 880_882delTT). The FUT2 genotypes identified were: 2 cases of Se³⁵⁷/Se^{357, 716} and 4 cases of Se³⁵⁷/Se³⁵⁷. Additionally, one sample revealed a novel heterozygous mutation, 818C>T, in exon 7 of the ABO gene, which was confirmed by PacBio sequencing to be located on the O haplotype. Conclusion PacBio sequencing technology demonstrates significant advantages in analyzing the haplotypes of para-Bombay blood type genes. This approach supports the establishment of a robust system for the identification of challenging blood types and provides novel evidence for precise transfusion practices in cancer patients.
Humans ; Neoplasms/genetics* ; Fucosyltransferases/genetics* ; ABO Blood-Group System/genetics* ; Male ; High-Throughput Nucleotide Sequencing/methods* ; Galactoside 2-alpha-L-fucosyltransferase ; Female ; Retrospective Studies ; Genotype ; Middle Aged ; Blood Grouping and Crossmatching/methods* ; Adult ; Mutation ; Aged

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

Objective This study aims to achieve high-yield functional expression of the human voltage-gated potassium channel K_V3.1 using an Escherichia coli cell-free protein synthesis system, thereby providing a novel synthetic approach for drug screening, structural analysis and functional characterization of K_V3.1. Methods K_V3.1 was expressed in an Escherichia coli cell-free protein synthesis system for 10 hours in the presence of peptide surfactant A₆K. The secondary structure of K_V3.1 was analyzed by circular dichroism spectroscopy. The potassium channel activity of the recombinant protein liposome K_V3.1-A₆K was investigated using fluorescent dyes Oxonol VI as indicators, which are capable of reflecting alterations in membrane potential. Results Soluble K_V3.1 protein was successfully synthesized, achieving a purified yield of up to 1.2 mg/mL via an Escherichia coli cell-free protein synthesis system. Circular dichroism spectroscopy revealed that K_V3.1 exhibited characteristic α-helical secondary structures. Membrane potential fluorescence assays demonstrated that the K_V3.1-A₆K proteoliposomes, which were reconstructed with surfactant peptide A₆K, exhibited remarkable potassium ion permeability. Conclusion This study successfully achieved high-yield expression of human K_V3.1 with activity using an Escherichia coli-based cell-free protein synthesis system. This innovative method not only significantly enhances the expression yield of K_V3.1, but also maintains its functional activity, thereby establishing a novel and efficient synthetic platform for drug screening and advancing our understanding of structure-function relationships in K_V3.1 research.
Humans ; Escherichia coli/metabolism* ; Shaw Potassium Channels/biosynthesis* ; Cell-Free System ; Circular Dichroism ; Protein Biosynthesis ; Recombinant Proteins/metabolism* ; Membrane Potentials ; Shab Potassium Channels